In this editorial,we comment on three articles published in a recent issue of World Journal of Gastroenterology.There is a pressing need for new research on autophagy's role in gastrointestinal(GI)disorders,and al...In this editorial,we comment on three articles published in a recent issue of World Journal of Gastroenterology.There is a pressing need for new research on autophagy's role in gastrointestinal(GI)disorders,and also novel insights into some liver conditions,such as metabolic dysfunction-associated fatty liver disease(MAFLD)and acute liver failure(ALF).Despite advancements,understanding autophagy's intricate mechanisms and implications in these diseases remains incomplete.Moreover,MAFLD's pathogenesis,encompassing hepatic steatosis and metabolic dysregulation,require further elucidation.Similarly,the mechanisms underlying ALF,a severe hepatic dysfunction,are poorly understood.Innovative studies exploring the interplay between autophagy and GI disorders,as well as defined mechanisms of MAFLD and ALF,are crucial for identifying therapeutic targets and enhancing diagnostic and treatment strategies to mitigate the global burden of these diseases.展开更多
BACKGROUND Acute non-variceal upper gastrointestinal bleeding(ANVUGIB)constitutes a prevalent emergency within Gastroenterology,encompassing 80%-90%of all gastrointestinal hemorrhage incidents.This condition is distin...BACKGROUND Acute non-variceal upper gastrointestinal bleeding(ANVUGIB)constitutes a prevalent emergency within Gastroenterology,encompassing 80%-90%of all gastrointestinal hemorrhage incidents.This condition is distinguished by its abrupt onset,swift progression,and notably elevated mortality rate.AIM To gather clinical data from patients with ANVUGIB at our hospital in order to elucidate the clinical characteristics specific to our institution and analyze the therapeutic effectiveness of endoscopic hemostasis.METHODS We retrospectively retrieved the records of 532 patients diagnosed with ANVUGIB by endoscopy at our hospital between March 2021 and March 2023,utilizing our medical record system.Data pertaining to general patient information,etiological factors,disease outcomes,and other relevant variables were meticulously collected and analyzed.RESULTS Among the 532 patients diagnosed with ANVUGIB,the male-to-female ratio was 2.91:1,with a higher prevalence among males.Notably,43.6%of patients presented with black stool as their primary complaint,while 27.4%had hematemesis as their initial symptom.Upon admission,17%of patients exhibited both hematemesis and black stool,while most ANVUGIB patients primarily complained of overt gastrointestinal bleeding.Urgent routine blood examinations at admission revealed that 75.8%of patients had anemia,with 63.4%experiencing moderate to severe anemia,and 1.5%having extremely severe anemia(hemoglobin<30 g/L).With regard to etiology,53.2%of patients experienced bleeding without a definitive trigger,24.2%had a history of using gastric mucosa-irritating medications,24.2%developed bleeding after alcohol consumption,2.8%attributed it to improper diet,1.7%to emotional excitement,and 2.3%to fatigue preceding the bleeding episode.Drug-induced ANVUGIB was more prevalent in the elderly than middle-aged and young individuals,while bleeding due to alcohol consumption showed the opposite trend.Additionally,diet-related bleeding was more common among the young age group compared to the middle-aged group.Gastrointestinal endoscopy identified peptic ulcers as the most frequent cause of ANVUGIB(73.3%),followed by gastrointestinal malignancies(10.9%),acute gastric mucous lesions(9.8%),and androgenic upper gastrointestinal bleeding(1.5%)among inpatients with ANVUGIB.Of the 532 patients with gastrointestinal bleeding,68 underwent endoscopic hemostasis,resulting in an endoscopic treatment rate of 12.8%,with a high immediate hemostasis success rate of 94.1%.展开更多
Objective: To assess the relation between acute gastrointestinal disease and Helicobacter pylori (H. pylori) infections. Methods: Over the 18-month period, a total of 323 patients referred to three hospitals in Babol ...Objective: To assess the relation between acute gastrointestinal disease and Helicobacter pylori (H. pylori) infections. Methods: Over the 18-month period, a total of 323 patients referred to three hospitals in Babol (north of Iran) were enrolled in this cross-sectional study. H. pylori status (rapid urease test), endoscopic findings in the patients, personal habits (smoking or alcohol intake) and administration of drugs, such as non-steroidal anti-inflammatory drugs (NSAIDs) were analyzed using standard Chi-square test and multinomial logistic regression analysis. Results: Results showed that acute gastric ulcer patients had a significant association with alcohol (P=0.001, OR=6.183), opium (P=0.022, OR=2.823), smoking (P=0.016, OR=2.579) and NSAIDs (P=0.046, OR=2.071). However, patients with in acute duodenal ulcer have a significant association with opium (P=0.023, OR=2.326) and alcohol (P=0.003, OR=3.888). As well as, gastric cancer had significant association with alcohol (P<0.05, OR=6.937), smoking (P=0.012, OR=2.738), family history (P=0.005, OR=4.380) and gender (P≤0.05, OR=5.103). Conclusions: Current investigation shows that H. pylori infection, alcoholism, male gender, age and family history have an additive impact on the incidence of gastric cancer. In addition, alcoholism, opium usage, NSAIDs and family history have more impact on the incidence of acute gastric ulcer and acute duodenal ulcer in patients.展开更多
Here,we report a case of fulminant gastrointestinal graft-versus-host disease(GI-GVHD) with cytomegalovirus(CMV) infection in 44-year-old woman.Despite the difficulties associated with the treatment of GIGVHD and GI-C...Here,we report a case of fulminant gastrointestinal graft-versus-host disease(GI-GVHD) with cytomegalovirus(CMV) infection in 44-year-old woman.Despite the difficulties associated with the treatment of GIGVHD and GI-CMV disease,the mucosal findings and the clinical course showed marked improvements during long-term clinical observation.The endoscopic findings were remarkable,with diffuse sloughing mucosa in the stomach and highly active inflammation and deep discrete ulcers throughout the colon.Changes in the CMV quantitative polymerase chain reaction results were correlated with the endoscopic mucosal findings and were useful for assessing the efficacy of the treatment.Although a definite diagnosis of GI-GVHD is generally made by endoscopy with biopsy,the gross appearance of this disease can vary depending on the endoscopy.In this paper,we also conduct a literature review of patients with GI-GVHD.展开更多
The red blood cell distribution width(RDW) is a routinely measured and automatically reported blood parameter,which reflects the degree of anisocytosis. Recently,the baseline RDW was found to have clinical significanc...The red blood cell distribution width(RDW) is a routinely measured and automatically reported blood parameter,which reflects the degree of anisocytosis. Recently,the baseline RDW was found to have clinical significance for assessing clinical outcome and severity of various pathological conditions including cardiovascular diseases,sepsis,cancers,leukemia,renal dysfunction and respiratory diseases. A myriad of factors,most of which ill-defined,have an impact on the red cell population dynamics(i.e.,production,maturation and turnover). A delay in the red blood cell clearance in pathological conditions represents one of the leading determinants of increased anisocytosis. Further study of RDW may reveal new insight into inflammation mechanisms. In this review,we specifically discuss the current literature about the association of RDW in various disease conditions involving the gastrointestinal and hepatobiliary systems. We also present some of the related measurements for their value in predicting clinical outcomes in such conditions. According to our data,RDW was found to be a valuable prognostic index in gastrointestinal disorders along with additional inflammatory biomarkers(i.e.,C reactive protein,erythrocyte sedimentation rate,and platelet count) and current disease severity indices used in clinical practice.展开更多
TREATMENT STRATEGIES FOR ACUTE VARICEAL BLEEDINGBackgoundAcute variceal bleeding has a significant mortality which ranges form 5% to 50% in patients with cirrhosis[1].Overall survival is probably improving,because of ...TREATMENT STRATEGIES FOR ACUTE VARICEAL BLEEDINGBackgoundAcute variceal bleeding has a significant mortality which ranges form 5% to 50% in patients with cirrhosis[1].Overall survival is probably improving,because of new therapeutic approaches,and improved medical care.However,mortality is still closely related to failure to control hacmorrhage or carly rebleeding,which is a distinct characteristic of portal hypertensive bleeding and occures in as many as 50% of patients in the first days to 6 weeks after admission et al[2].展开更多
Endoscopic clipping has been established as a safe and effective method for the treatment of nonvariceal upper gastrointestinal bleeding in numerous randomized studies.Recently,clipping has been applied to various les...Endoscopic clipping has been established as a safe and effective method for the treatment of nonvariceal upper gastrointestinal bleeding in numerous randomized studies.Recently,clipping has been applied to various lesions in the lower gastrointestinal tract,including diverticular bleeding,postpolypectomy bleeding,and repair of perforations with successful outcomes.We review the safety and efficacy of this maneuver for the management of diseases in the lower gastrointestinal tract.展开更多
Six patients treated with human leukocyte antigen (HLA)-mismatched bone marrow transplantation (BMT) suffered from grade I to IV acute graft-versus-host disease (aGvHD) after engrafting. Up to date, 4 patients with gr...Six patients treated with human leukocyte antigen (HLA)-mismatched bone marrow transplantation (BMT) suffered from grade I to IV acute graft-versus-host disease (aGvHD) after engrafting. Up to date, 4 patients with grade I to II GvHD have lived for over 2920, 910, 740 and 680 days, respectively. Two other patients died of grade IV hyperacute GvHD. The results seem to indicate that patients in mismatched BMT have a high incidence of aGvHD within a month. The severity of aGvHD is positively correlated with the degree of HLA mismatching. The higher the degree of mismatch of HLA, the earlier and the more severe the aGvHD occurrs. The cutaneous lesion of the patient with GvHD is severe and of ten complicated by mucositis. Lethal hyperacute GvHD must be considered when a patient shows following signs at beginning: (1) The symptoms appear early (within 2weeks) ;(2) peripheral white blood cell count does not recover (<0. 5×109/L) to normal; and (3) high fever persists. In the epidermal ultrastructure of patients, besides acantholysis, autophagic degeneration of keratinocytes,and satellite cell dyskeratosis, there were scattered necrotic keratinocytes, breaking and thickening of basal membrane and presence of a lot of pigment in the intercellular space. These imply that the ultrastructural damages in the skin of patients with aGvHD after mismatched transplantation are more severe than after matched ones.展开更多
This study aimed to explore macrophage polarization in acute graft-versus-host disease after hematopoietic stem cell transplantation, and investigated if arsenic trioxide(ATO) could correct this imbalance. In the colo...This study aimed to explore macrophage polarization in acute graft-versus-host disease after hematopoietic stem cell transplantation, and investigated if arsenic trioxide(ATO) could correct this imbalance. In the colon of GVHD mice, we found that the number of F4/80+iNOS+ cells as well as the expression intensity of TNF-α and IL-1β was greater in the GVHD group than in the BM group, whereas the number of F4/80+CD206+ cells and the expression intensity of IL-10 and TGF-β was greater in the BM group than in the GVHD group. We investigated the effect of ATO on GVHD mice, and found that ATO treatment clearly improved the survival of the mice and reduced the severity of GVHD. In addition, ATO reduced the number of F4/80+iNOS+ cells, and increased the number of F4/80+CD206+ cells in the colon of GVHD mice. Furthermore, ATO sharply decreased CD86 and CD80 expression, and increased CD163 and CD206 expression in macrophages induced from aGVHD patients. Therefore,ATO can modulate the M1 and M2 phenotype in GVHD mice or in macrophages from aGVHD patients. Our data suggest that macrophage polarization is involved in the pathogenesis of aGVHD, and ATO treatment modulates macrophage polarization toward an M2 phenotype.展开更多
Chronic graft-versus-host disease(cGVHD)is a major complication following unmanipulated haploidentical hematopoietic stem cell transplantation(haplo-HSCT).We aimed to identify the risk factors for cGVHD in patients wh...Chronic graft-versus-host disease(cGVHD)is a major complication following unmanipulated haploidentical hematopoietic stem cell transplantation(haplo-HSCT).We aimed to identify the risk factors for cGVHD in patients who underwent anti-thymocyte globulin-based haplo-HSCT for acute myeloid leukemia(n=280).The diagnosis of cGVHD was in accordance with the National Institutes of Health consensus criteria.A total of 169 patients suffered from cGVHD.The patients who had 3 loci mismatched had a higher 8-year incidence of cGVHD(total,66.0%vs.53.7%,P=0.031;moderate to severe,42.4%vs.30.1%,P=0.036)than the patients who had 1 to 2 loci mismatched.The patients who had maternal donors had a higher 8-year incidence of moderate to severe cGVHD(49.2%vs.32.9%,P=0.024)compared with the patients who had other donors.The patients who had grades III to IV acute GVHD(aGVHD)had higher 8-year incidence of cGVHD(total,88.0%vs.50.4%,P<0.001;moderate to severe,68.0%vs.27.0%,P<0.001)compared with the patients without aGVHD.In multivariate analysis,grades III to IV aGVHD was the only independent risk factor for cGVHD.Thus,further interventions should be considered in patients with severe aGVHD to prevent cGVHD.展开更多
To explore the effect and pathogenssis of acute graft-versus-host disease (aGVHD) on early diffuse lung injury in allogeneic hematopoietic stem cell transplantation (allo-HSCT), we established an aGVHD model of C57BL/...To explore the effect and pathogenssis of acute graft-versus-host disease (aGVHD) on early diffuse lung injury in allogeneic hematopoietic stem cell transplantation (allo-HSCT), we established an aGVHD model of C57BL/6→BALB/c mice. Chest computed tomography (CT) scans, histopathology and the levels of cytokines including tumor necrosis factor α (TNFα) and Interferon (IFNγ) in lungs were dynamically detected in recipient mice after transplantation. The incidence of aGVHD was respectively 0%, 0% and 100% in simple irradiation group (A), syngeneic transplant group(B) and allogeneic transplant group (C). Chest CT scans of recipient mice were normal in 3 groups on days +3 and +7 after transplantation. CT showed that two of ten mice had bilateral lung diffuse infiltrate on day +12 (on the brink of death) in group A and 6 of 10 mice had bilateral lung diffuse infiltrate on day +14 (3 d after aGVHD occurring) in group C, and were normal on days +12 and +14 in group B after transplantation. Histopathology of lungs in the 3 groups was similar, consisting of minor interstitial pneumonitis on day +3. Group A showed edema, hyperplasia of epithelial cells and widened alveolar interval on day +7, and epithelial cell necrosis, lymphocyte infiltration, hemorrhage, protein leakage, and local consolidation on day +12. The histopathology of group B showed slight edema of epithelial cells on +7 day, which were slighter than that on day +3, and virtually normal on day +14. The histopathology in group C was characterized by the significant expansion and congestion of capillaries, and lymphocyte infiltration on day +7, the acute pneumonitis was present involving tissue edema, lymphocyte and macrophage infiltration, protein leakage and perivascular inflammation on day +14. In group A, the levels of TNFα were lower on day +7 than on day +3. In group B, the levels of TNFα attained a peak on day +3, which decreased on days +7 and +14. In group C, the levels of TNFα were highest on day +7 and there was a significant difference between those on days +7 and +14 (P=0.816). In group A, the levels of IFNγ on day +7 were higher than on day +3. In group B, the levels of IFNγ increased progressively, but the comparison of IFNγ levels in different times had no statistical significance (P=0.521, 0.118, 0.340). In group C, the levels of IFNγ attained a peak by day +7 and decreased on day +14. aGVHD is the main cause of early non-infectious lung injury. T lymphocytes and TNFα are possibly implicated in the pathogenesis of acute GVHD-induced lung injury. The decreased levels of IFNγ in lung tissues following transplantation might be associated with pulmonary fibrosis in late non-infectious pulmonary complications.展开更多
Accumulating evidence suggests that a reduction in the number of Foxp3^(+) regulatory T cells(Tregs)contributes to the pathogenesis of acute graft-versus-host disease(aGVHD),which is a major adverse complication that ...Accumulating evidence suggests that a reduction in the number of Foxp3^(+) regulatory T cells(Tregs)contributes to the pathogenesis of acute graft-versus-host disease(aGVHD),which is a major adverse complication that can occur after allogeneic hematopoietic stem cell transplantation(allo-HSCT).However,the precise features and mechanism underlying the defects in Tregs remain largely unknown.In this study,we demonstrated that Tregs were more dramatically decreased in bone marrow compared with those in peripheral blood from aGVHD patients and that bone marrow Treg defects were negatively associated with hematopoietic reconstitution.Tregs from aGVHD patients exhibited multiple defects,including the instability of Foxp3 expression,especially in response to IL-12,impaired suppressor function,decreased migratory capacity,and increased apoptosis.Transcriptional profiling revealed the downregulation of Lkb1,a previously identified critical regulator of murine Treg identity and metabolism,and murine Lkb1-regulated genes in Tregs from aGVHD patients.Foxp3 expression in human Tregs could be decreased and increased by the knockdown and overexpression of the Lkb1 gene,respectively.Furthermore,a loss-of-function assay in an aGVHD murine model confirmed that Lkb1 deficiency could impair Tregs and aggravate disease severity.These findings reveal that Lkb1 downregulation contributes to multiple defects in Tregs in human aGVHD and highlight the Lkb1-related pathways that could serve as therapeutic targets that may potentially be manipulated to mitigate aGVHD.展开更多
基金Supported by the European Union-NextGenerationEU,through The National Recovery and Resilience Plan of The Republic of Bulgaria,No.BG-RRP-2.004-0008。
文摘In this editorial,we comment on three articles published in a recent issue of World Journal of Gastroenterology.There is a pressing need for new research on autophagy's role in gastrointestinal(GI)disorders,and also novel insights into some liver conditions,such as metabolic dysfunction-associated fatty liver disease(MAFLD)and acute liver failure(ALF).Despite advancements,understanding autophagy's intricate mechanisms and implications in these diseases remains incomplete.Moreover,MAFLD's pathogenesis,encompassing hepatic steatosis and metabolic dysregulation,require further elucidation.Similarly,the mechanisms underlying ALF,a severe hepatic dysfunction,are poorly understood.Innovative studies exploring the interplay between autophagy and GI disorders,as well as defined mechanisms of MAFLD and ALF,are crucial for identifying therapeutic targets and enhancing diagnostic and treatment strategies to mitigate the global burden of these diseases.
基金Supported by Xi’an Health Commission Residential Training Base Construction Project,No.2023zp09.
文摘BACKGROUND Acute non-variceal upper gastrointestinal bleeding(ANVUGIB)constitutes a prevalent emergency within Gastroenterology,encompassing 80%-90%of all gastrointestinal hemorrhage incidents.This condition is distinguished by its abrupt onset,swift progression,and notably elevated mortality rate.AIM To gather clinical data from patients with ANVUGIB at our hospital in order to elucidate the clinical characteristics specific to our institution and analyze the therapeutic effectiveness of endoscopic hemostasis.METHODS We retrospectively retrieved the records of 532 patients diagnosed with ANVUGIB by endoscopy at our hospital between March 2021 and March 2023,utilizing our medical record system.Data pertaining to general patient information,etiological factors,disease outcomes,and other relevant variables were meticulously collected and analyzed.RESULTS Among the 532 patients diagnosed with ANVUGIB,the male-to-female ratio was 2.91:1,with a higher prevalence among males.Notably,43.6%of patients presented with black stool as their primary complaint,while 27.4%had hematemesis as their initial symptom.Upon admission,17%of patients exhibited both hematemesis and black stool,while most ANVUGIB patients primarily complained of overt gastrointestinal bleeding.Urgent routine blood examinations at admission revealed that 75.8%of patients had anemia,with 63.4%experiencing moderate to severe anemia,and 1.5%having extremely severe anemia(hemoglobin<30 g/L).With regard to etiology,53.2%of patients experienced bleeding without a definitive trigger,24.2%had a history of using gastric mucosa-irritating medications,24.2%developed bleeding after alcohol consumption,2.8%attributed it to improper diet,1.7%to emotional excitement,and 2.3%to fatigue preceding the bleeding episode.Drug-induced ANVUGIB was more prevalent in the elderly than middle-aged and young individuals,while bleeding due to alcohol consumption showed the opposite trend.Additionally,diet-related bleeding was more common among the young age group compared to the middle-aged group.Gastrointestinal endoscopy identified peptic ulcers as the most frequent cause of ANVUGIB(73.3%),followed by gastrointestinal malignancies(10.9%),acute gastric mucous lesions(9.8%),and androgenic upper gastrointestinal bleeding(1.5%)among inpatients with ANVUGIB.Of the 532 patients with gastrointestinal bleeding,68 underwent endoscopic hemostasis,resulting in an endoscopic treatment rate of 12.8%,with a high immediate hemostasis success rate of 94.1%.
文摘Objective: To assess the relation between acute gastrointestinal disease and Helicobacter pylori (H. pylori) infections. Methods: Over the 18-month period, a total of 323 patients referred to three hospitals in Babol (north of Iran) were enrolled in this cross-sectional study. H. pylori status (rapid urease test), endoscopic findings in the patients, personal habits (smoking or alcohol intake) and administration of drugs, such as non-steroidal anti-inflammatory drugs (NSAIDs) were analyzed using standard Chi-square test and multinomial logistic regression analysis. Results: Results showed that acute gastric ulcer patients had a significant association with alcohol (P=0.001, OR=6.183), opium (P=0.022, OR=2.823), smoking (P=0.016, OR=2.579) and NSAIDs (P=0.046, OR=2.071). However, patients with in acute duodenal ulcer have a significant association with opium (P=0.023, OR=2.326) and alcohol (P=0.003, OR=3.888). As well as, gastric cancer had significant association with alcohol (P<0.05, OR=6.937), smoking (P=0.012, OR=2.738), family history (P=0.005, OR=4.380) and gender (P≤0.05, OR=5.103). Conclusions: Current investigation shows that H. pylori infection, alcoholism, male gender, age and family history have an additive impact on the incidence of gastric cancer. In addition, alcoholism, opium usage, NSAIDs and family history have more impact on the incidence of acute gastric ulcer and acute duodenal ulcer in patients.
基金Supported by Grant from the National Center for Global Health and Medicine
文摘Here,we report a case of fulminant gastrointestinal graft-versus-host disease(GI-GVHD) with cytomegalovirus(CMV) infection in 44-year-old woman.Despite the difficulties associated with the treatment of GIGVHD and GI-CMV disease,the mucosal findings and the clinical course showed marked improvements during long-term clinical observation.The endoscopic findings were remarkable,with diffuse sloughing mucosa in the stomach and highly active inflammation and deep discrete ulcers throughout the colon.Changes in the CMV quantitative polymerase chain reaction results were correlated with the endoscopic mucosal findings and were useful for assessing the efficacy of the treatment.Although a definite diagnosis of GI-GVHD is generally made by endoscopy with biopsy,the gross appearance of this disease can vary depending on the endoscopy.In this paper,we also conduct a literature review of patients with GI-GVHD.
文摘The red blood cell distribution width(RDW) is a routinely measured and automatically reported blood parameter,which reflects the degree of anisocytosis. Recently,the baseline RDW was found to have clinical significance for assessing clinical outcome and severity of various pathological conditions including cardiovascular diseases,sepsis,cancers,leukemia,renal dysfunction and respiratory diseases. A myriad of factors,most of which ill-defined,have an impact on the red cell population dynamics(i.e.,production,maturation and turnover). A delay in the red blood cell clearance in pathological conditions represents one of the leading determinants of increased anisocytosis. Further study of RDW may reveal new insight into inflammation mechanisms. In this review,we specifically discuss the current literature about the association of RDW in various disease conditions involving the gastrointestinal and hepatobiliary systems. We also present some of the related measurements for their value in predicting clinical outcomes in such conditions. According to our data,RDW was found to be a valuable prognostic index in gastrointestinal disorders along with additional inflammatory biomarkers(i.e.,C reactive protein,erythrocyte sedimentation rate,and platelet count) and current disease severity indices used in clinical practice.
文摘TREATMENT STRATEGIES FOR ACUTE VARICEAL BLEEDINGBackgoundAcute variceal bleeding has a significant mortality which ranges form 5% to 50% in patients with cirrhosis[1].Overall survival is probably improving,because of new therapeutic approaches,and improved medical care.However,mortality is still closely related to failure to control hacmorrhage or carly rebleeding,which is a distinct characteristic of portal hypertensive bleeding and occures in as many as 50% of patients in the first days to 6 weeks after admission et al[2].
文摘Endoscopic clipping has been established as a safe and effective method for the treatment of nonvariceal upper gastrointestinal bleeding in numerous randomized studies.Recently,clipping has been applied to various lesions in the lower gastrointestinal tract,including diverticular bleeding,postpolypectomy bleeding,and repair of perforations with successful outcomes.We review the safety and efficacy of this maneuver for the management of diseases in the lower gastrointestinal tract.
文摘Six patients treated with human leukocyte antigen (HLA)-mismatched bone marrow transplantation (BMT) suffered from grade I to IV acute graft-versus-host disease (aGvHD) after engrafting. Up to date, 4 patients with grade I to II GvHD have lived for over 2920, 910, 740 and 680 days, respectively. Two other patients died of grade IV hyperacute GvHD. The results seem to indicate that patients in mismatched BMT have a high incidence of aGvHD within a month. The severity of aGvHD is positively correlated with the degree of HLA mismatching. The higher the degree of mismatch of HLA, the earlier and the more severe the aGvHD occurrs. The cutaneous lesion of the patient with GvHD is severe and of ten complicated by mucositis. Lethal hyperacute GvHD must be considered when a patient shows following signs at beginning: (1) The symptoms appear early (within 2weeks) ;(2) peripheral white blood cell count does not recover (<0. 5×109/L) to normal; and (3) high fever persists. In the epidermal ultrastructure of patients, besides acantholysis, autophagic degeneration of keratinocytes,and satellite cell dyskeratosis, there were scattered necrotic keratinocytes, breaking and thickening of basal membrane and presence of a lot of pigment in the intercellular space. These imply that the ultrastructural damages in the skin of patients with aGvHD after mismatched transplantation are more severe than after matched ones.
基金supported by the National Key Research and Development Program of China (2017YFA0105500 and 2017YFA0105503)the Beijing Natural Science Foundation (H2018206423)+4 种基金the Key Program of the National Natural Science Foundation of China (81730004)the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (81621001)the National Natural Science Foundation of China (81670116)the Beijing Natural Science Foundation (7171013)he Beijing Municipal Science and Technology Commission (Z171100001017084)。
文摘This study aimed to explore macrophage polarization in acute graft-versus-host disease after hematopoietic stem cell transplantation, and investigated if arsenic trioxide(ATO) could correct this imbalance. In the colon of GVHD mice, we found that the number of F4/80+iNOS+ cells as well as the expression intensity of TNF-α and IL-1β was greater in the GVHD group than in the BM group, whereas the number of F4/80+CD206+ cells and the expression intensity of IL-10 and TGF-β was greater in the BM group than in the GVHD group. We investigated the effect of ATO on GVHD mice, and found that ATO treatment clearly improved the survival of the mice and reduced the severity of GVHD. In addition, ATO reduced the number of F4/80+iNOS+ cells, and increased the number of F4/80+CD206+ cells in the colon of GVHD mice. Furthermore, ATO sharply decreased CD86 and CD80 expression, and increased CD163 and CD206 expression in macrophages induced from aGVHD patients. Therefore,ATO can modulate the M1 and M2 phenotype in GVHD mice or in macrophages from aGVHD patients. Our data suggest that macrophage polarization is involved in the pathogenesis of aGVHD, and ATO treatment modulates macrophage polarization toward an M2 phenotype.
文摘Chronic graft-versus-host disease(cGVHD)is a major complication following unmanipulated haploidentical hematopoietic stem cell transplantation(haplo-HSCT).We aimed to identify the risk factors for cGVHD in patients who underwent anti-thymocyte globulin-based haplo-HSCT for acute myeloid leukemia(n=280).The diagnosis of cGVHD was in accordance with the National Institutes of Health consensus criteria.A total of 169 patients suffered from cGVHD.The patients who had 3 loci mismatched had a higher 8-year incidence of cGVHD(total,66.0%vs.53.7%,P=0.031;moderate to severe,42.4%vs.30.1%,P=0.036)than the patients who had 1 to 2 loci mismatched.The patients who had maternal donors had a higher 8-year incidence of moderate to severe cGVHD(49.2%vs.32.9%,P=0.024)compared with the patients who had other donors.The patients who had grades III to IV acute GVHD(aGVHD)had higher 8-year incidence of cGVHD(total,88.0%vs.50.4%,P<0.001;moderate to severe,68.0%vs.27.0%,P<0.001)compared with the patients without aGVHD.In multivariate analysis,grades III to IV aGVHD was the only independent risk factor for cGVHD.Thus,further interventions should be considered in patients with severe aGVHD to prevent cGVHD.
基金Supported by the National Natural Science Foundation of China (Grant No. 30971300)
文摘To explore the effect and pathogenssis of acute graft-versus-host disease (aGVHD) on early diffuse lung injury in allogeneic hematopoietic stem cell transplantation (allo-HSCT), we established an aGVHD model of C57BL/6→BALB/c mice. Chest computed tomography (CT) scans, histopathology and the levels of cytokines including tumor necrosis factor α (TNFα) and Interferon (IFNγ) in lungs were dynamically detected in recipient mice after transplantation. The incidence of aGVHD was respectively 0%, 0% and 100% in simple irradiation group (A), syngeneic transplant group(B) and allogeneic transplant group (C). Chest CT scans of recipient mice were normal in 3 groups on days +3 and +7 after transplantation. CT showed that two of ten mice had bilateral lung diffuse infiltrate on day +12 (on the brink of death) in group A and 6 of 10 mice had bilateral lung diffuse infiltrate on day +14 (3 d after aGVHD occurring) in group C, and were normal on days +12 and +14 in group B after transplantation. Histopathology of lungs in the 3 groups was similar, consisting of minor interstitial pneumonitis on day +3. Group A showed edema, hyperplasia of epithelial cells and widened alveolar interval on day +7, and epithelial cell necrosis, lymphocyte infiltration, hemorrhage, protein leakage, and local consolidation on day +12. The histopathology of group B showed slight edema of epithelial cells on +7 day, which were slighter than that on day +3, and virtually normal on day +14. The histopathology in group C was characterized by the significant expansion and congestion of capillaries, and lymphocyte infiltration on day +7, the acute pneumonitis was present involving tissue edema, lymphocyte and macrophage infiltration, protein leakage and perivascular inflammation on day +14. In group A, the levels of TNFα were lower on day +7 than on day +3. In group B, the levels of TNFα attained a peak on day +3, which decreased on days +7 and +14. In group C, the levels of TNFα were highest on day +7 and there was a significant difference between those on days +7 and +14 (P=0.816). In group A, the levels of IFNγ on day +7 were higher than on day +3. In group B, the levels of IFNγ increased progressively, but the comparison of IFNγ levels in different times had no statistical significance (P=0.521, 0.118, 0.340). In group C, the levels of IFNγ attained a peak by day +7 and decreased on day +14. aGVHD is the main cause of early non-infectious lung injury. T lymphocytes and TNFα are possibly implicated in the pathogenesis of acute GVHD-induced lung injury. The decreased levels of IFNγ in lung tissues following transplantation might be associated with pulmonary fibrosis in late non-infectious pulmonary complications.
基金by grants from the National Basic Research Program of China(2015CB964402)the National Natural Science Foundation of China(81670171,81601369)+2 种基金the CAMS Innovation Fund for Medical Sciences(CIFMS,2016-I2M-1-003 and 2018-I2M-HL-013)the Tianjin Science Funds for Distinguished Young Scholars(17JCJQJC45800)the Nonprofit Central Research Institute Fund of the Chinese Academy of Medical Sciences(2018PT32034 and 2019-RC-HL-013).
文摘Accumulating evidence suggests that a reduction in the number of Foxp3^(+) regulatory T cells(Tregs)contributes to the pathogenesis of acute graft-versus-host disease(aGVHD),which is a major adverse complication that can occur after allogeneic hematopoietic stem cell transplantation(allo-HSCT).However,the precise features and mechanism underlying the defects in Tregs remain largely unknown.In this study,we demonstrated that Tregs were more dramatically decreased in bone marrow compared with those in peripheral blood from aGVHD patients and that bone marrow Treg defects were negatively associated with hematopoietic reconstitution.Tregs from aGVHD patients exhibited multiple defects,including the instability of Foxp3 expression,especially in response to IL-12,impaired suppressor function,decreased migratory capacity,and increased apoptosis.Transcriptional profiling revealed the downregulation of Lkb1,a previously identified critical regulator of murine Treg identity and metabolism,and murine Lkb1-regulated genes in Tregs from aGVHD patients.Foxp3 expression in human Tregs could be decreased and increased by the knockdown and overexpression of the Lkb1 gene,respectively.Furthermore,a loss-of-function assay in an aGVHD murine model confirmed that Lkb1 deficiency could impair Tregs and aggravate disease severity.These findings reveal that Lkb1 downregulation contributes to multiple defects in Tregs in human aGVHD and highlight the Lkb1-related pathways that could serve as therapeutic targets that may potentially be manipulated to mitigate aGVHD.